The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation

Hiba Ahmad Zahreddine, Biljana Culjkovic-Kraljacic, Sarit Assouline, Patrick Gendron, Andrea A. Romeo, Stephen J. Morris, Gregory Cormack, James B. Jaquith, Leandro Cerchietti, Eftihia Cocolakis, Abdellatif Amri, Julie Bergeron, Brian Leber, Michael W. Becker, Shanshan Pei, Craig T. Jordan, Wilson H. Miller and Katherine L. B. Borden ()
Additional contact information
Hiba Ahmad Zahreddine: Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada
Biljana Culjkovic-Kraljacic: Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada
Sarit Assouline: Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, 3755 Côte-Ste-Catherine Road, Montréal, Québec H3T 1E2, Canada
Patrick Gendron: Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada
Andrea A. Romeo: Pharmascience Inc., 6111 Royalmount Avenue, Montreal, Quebec H4P 2T4, Canada
Stephen J. Morris: Pharmascience Inc., 6111 Royalmount Avenue, Montreal, Quebec H4P 2T4, Canada
Gregory Cormack: Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada
James B. Jaquith: Pharmascience Inc., 6111 Royalmount Avenue, Montreal, Quebec H4P 2T4, Canada
Leandro Cerchietti: Weill Cornell Medical College, Cornell University, 1305 York Avenue, New York, New York 10021, USA
Eftihia Cocolakis: Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, 3755 Côte-Ste-Catherine Road, Montréal, Québec H3T 1E2, Canada
Abdellatif Amri: Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada
Julie Bergeron: Hôpital Maisonneuve-Rosemont, 5415 Boulevard de l’Assomption, Montréal, Québec H1T 2M4, Canada
Brian Leber: McMaster University/Hamilton Health Sciences, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada
Michael W. Becker: 601 Elmwood Avenue, University of Rochester
Shanshan Pei: University of Colorado Denver, 13123 East 16th Avenue, Aurora, Colorado 80045, USA
Craig T. Jordan: University of Colorado Denver, 13123 East 16th Avenue, Aurora, Colorado 80045, USA
Wilson H. Miller: Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, 3755 Côte-Ste-Catherine Road, Montréal, Québec H3T 1E2, Canada
Katherine L. B. Borden: Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada

Nature, 2014, vol. 511, issue 7507, 90-93

Abstract: A new mechanism by which acute myeloid leukaemia patients become resistant to Ara-C and a newer treatment, ribavirin, is uncovered; these drugs can be glucuronidated and thereby inactivated by members of the UDP glucuronosyltransferase family of enzymes activated through GLI1 signalling.

Date: 2014
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DOI: 10.1038/nature13283

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